High throughput screening of mitochondrial bioenergetics in human differentiated myotubes identifies novel enhancers of muscle performance in aged mice

Mitochondrial dysfunction is increasingly recognized as a contributor to age-related muscle loss and functional impairment. Therefore, we developed a high throughput screening strategy that enabled the identification of compounds boosting mitochondrial energy production in a human skeletal muscle ce...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-06, Vol.8 (1), p.9408-12, Article 9408
Main Authors: Biesemann, Nadine, Ried, Janina S., Ding-Pfennigdorff, Danping, Dietrich, Axel, Rudolph, Christine, Hahn, Steffen, Hennerici, Wolfgang, Asbrand, Christian, Leeuw, Thomas, Strübing, Carsten
Format: Article
Language:English
Subjects:
13/106
13/95
14/63
38/39
38/5
38/77
631/154/1435/2417
631/443/7
631/80/304
64/60
82/80
9/10
Age
Bioenergetics
Drug discovery
Hesperidin
High-throughput screening
Humanities and Social Sciences
Mitochondria
multidisciplinary
Musculoskeletal system
Myotubes
Natural products
Oxidative stress
Oxygen consumption
Sarcopenia
Science
Science (multidisciplinary)
Skeletal muscle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mitochondrial dysfunction is increasingly recognized as a contributor to age-related muscle loss and functional impairment. Therefore, we developed a high throughput screening strategy that enabled the identification of compounds boosting mitochondrial energy production in a human skeletal muscle cell model. Screening of 7949 pure natural products revealed 22 molecules that significantly increased oxygen consumption and ATP levels in myotubes. One of the most potent compounds was the flavanone hesperetin. Hesperetin (10 µM) increased intracellular ATP by 33% and mitochondrial spare capacity by 25%. Furthermore, the compound reduced oxidative stress in primary myotubes as well as muscle tissue in vivo . In aged mice administration of hesperetin (50 mg/kg/d) completely reverted the age-related decrease of muscle fiber size and improved running performance of treated animals. These results provide a novel screening platform for the discovery of drugs that can improve skeletal muscle function in patients suffering from sarcopenia or other disorders associated with mitochondrial dysfunction.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-27614-8